13. puberty 2008 - the medical university of south … of reproduction/bor... · toward earlier...
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Puberty - sexual maturation
• transition from sexually immature child tosexually mature adult
• puberty from Latin 'pubes" meaning hair• varies with age, weight• in humans, begins earlier in females than
males• in western Europe and USA, clear trend
toward earlier puberty in girls and boys
Females - human
• 1st menstruation (menarche)12 years (7 - 19 yr)
• 1st ovulation– then or as much as 2 yrs latter– 1st menarche can be
anovulatory• menarche and ovulation are
steps in a series of changes• development of 2nd sex
characteristics
Secondary sex characteristics-Female
• uterus, oviducts and vagina grow and mature• pelvis grows• pubic and axillary hair• breast development• sweat and sebaceous glands increase activity• decrease in voice• increase in metabolic rate• fat deposition especially in hips and breasts• skeletal growth (usually ends about 16 years of age)
Males - human /1• growth spurt and fat deposition
– 10-13 yr girls taller & more developedthan same age boys
– later stimulation of growth due toincreasing testosterone
• testes and secondary sexcharacteristics– pubic hair and axilla, chest, facial and
extremities– sweat glands become active in scrotum,
face, back and chest– areola darkens and widens– vocal cords double in length = dramatic
deepening of voice
Males - human /2
• scrotum, penis growth– spontaneous erections increase in frequency
• occur in infants and fetuses• nocturnal emissions/ejaculation
– Normal• do not indicate abnormal behavior or physiology
– both spontaneous erections and nocturnalemissions decrease after puberty
Neonatal Gn and Androgen
• however, FSH & LH– can be at or near adult
levels soon after birthand for first 2 years oflife
– neonatal (0-5 months)boys have elevated Tlevels responsible forLeydig & Sertoli cellmitosis and futuresperm count
Hormones - Birth to PubertyEarly Puberty
• 9-12 yrs =– FSH then LH rise
• occurs in females 1 - 2 yrs earlier thanmales
– Prolactin rises in females but notmales• possibly due to rising estradiol
Hormones - Birth to PubertyFSH & LH
• During puberty fluctuation in LH andFSH great– role unknown– dramatic rise at night– daily cycle in not seen in adults or
children– from early to mid puberty dramatic
rise in magnitude and frequency ofLH surges
• sleep augmented LH secretion– in late puberty
• daytime surges also increase, butstill less than nighttime
– continues until adult-noncyclic-levelsachieved
Hormones - Birth to PubertyTestosterone /1
• Testosterone rises in boyswith increasing LH– elevated at night
• sleep augmented LH secretion– during mid puberty, T can also
be elevated during day– females show similar
increases but not the sameelevation as in males
Hormones - Birth to PubertyTestosterone /2
• Roles in males and females:– pubic and axillary hair growth– vocal cord growth– development of sebaceous glands– growth of long bones– protein anabolism - muscle growth– sex drive
Hormones - Birth to PubertyEstrogens /1
• estrogens are extremelyhigh in both males andfemales at birth– ~5000 pg/ml– Placental/maternal in origin– infants can show breast
budding and 'witches milk'– levels drop soon after birth
until puberty
Hormones - Birth to PubertyEstrogens /2
• in females– estrogens rise thru puberty until adult levels, follows LH
secretion• in boys
– estrone higher than estradiol– both lower than in girls, but rise with puberty
• in males– half of estradiol from extraglandular aromatization of
testosterone– a quarter or less from testicular synthesis
Hormones - Birth to PubertyEstrogens /3
• Roles in males and females:– bony pelvic growth– initial mammary gland growth
• gynecomastia in some boys - lost in 1-2 yrs– onset of fat deposition– long bone closure
• In females– growth of external genitalia– growth oviduct and uterus– continued growth of mammary glands
Hormones - Birth to PubertyAdrenal Hormones
• earliest detectable changes– proceeding gonadotropins and sex steroids
• progressive increase in adrenal androgens– dehydroepiandrosterone (DHEA)– DHEA sulfate
• glucocorticoids and mineralocorticoids donot increase
Hormones - Birth to Puberty ADRENARCHE
• Increasing adrenal steroids = ADRENARCHE– starts at about age 8– continues until 13 - 15 yr age
• DHEA/DHEA sulfate– orders of magnitude higher in plasma concentration than
sex steroids– role unknown but they do promote pubic and axillary hair
• growth spurt is not dependent on these androgens• not involved with timing puberty
Mechanisms Underlying Puberty
• Two hypotheses that are not mutuallyexclusive– gonadostat hypothesis– hypothalamic maturation
Gonadostat Hypothesis /1
• negative feedback of FSH and LH on thepituitary and hypothalamus is verysensitive [low threshold]
• very sensitive negative feedback = lowconcentrations of steroids
• at puberty, set point is increased,becoming less sensitive to steroids - thus,steroids in the plasma rise
Gonadostat Hypothesis /2
• pituitary response to steroids does changewith puberty
• however, changing steroids do not drivechange
• positive feedback established late inpuberty– >50% of the cycles in early post-puberty are
anovulatory– decreases to one fifth after 5 years
Hypothalamic Maturation /1
• currently accepted hypothesis– maturation of the CNS and increased
output of GnRH drives puberty• requires only changes in the GnRH
neurosecretory neurons– no changes in negative and positive
feedback required
Puberty - Genes
• Puberty is controlled by genetic and environmental factors• 17 different single-gene mutations
– Mutation leads to delayed or absent puberty in humans– Several of these genes
• involved in the development of the olfactory nervous system,• result in anosmia/hyposmia and hypogonadotropic hypogonadism
– otherwise known as Kallmann syndrome.
– Development of the gonadotropin-releasing hormone (GnRH)neurons
• responsible for regulating fertility• intricately associated with development of the olfactory system
• single-gene mutations are presently estimated to account forapproximately 30% of individuals with disorders of puberty
Herbison AE HORMONE RESEARCH 68 :75-79 2007
Hypothalamic Maturation /2
• pulsatile LH release at onset of puberty– even in gonadectomized monkeys
• in male rhesus gonadectomized at birth– pulsatile LH release
• levels normal for first 10 weeks of life (as in controls)– no release for 2.5 yrs - juvenile hiatus– pulsatile secretions begin on time and transition
to adult levels normally in absence of testes
Hypothalamic Maturation /3
• thus, puberty is ability to release pulses of GnRH• adult levels of steroids do not turn on GnRH pulse
system• clinical studies confirms that humans are similar
– first 6 months associated with fluctuating, often highplasma FSH, LH, T (boys), E (girls)
– by 1-2 yr age, system exhibits juvenile hiatus– Turner's syndrome girls - agonadal
• start puberty at correct time
Puberty - Kisspeptin
• product of the gene Kiss1• G-protein coupled receptor ligand for GPR54• Kiss1 was originally identified as a human
metastasis suppressor• Kiss-1 mRNA and steroid receptors
– Are coexpressed in KiSS-1 neurons– are direct target for the action of sex steroids– KiSS-1 mRNA and/or GPR54 mRNA expression increase
with puberty– electrophysiologic response of GnRH neurons to
kisspeptins increase over the course of puberty
Herbison AE HORMONE RESEARCH 68 :75-79 2007
Puberty - Kisspeptin• Kisspeptin-GPR54 signalling system
– affect puberty by directly or indirectly modulating the functioning ofthe GnRH neurons and pituitary gonadotrophs
Herbison AE HORMONE RESEARCH 68 :75-79 2007
Precocious Puberty
• precocious puberty– can occur as young as 2 yr age– pituitary and gonads can function in adult
manner– usually CNS tumor– But, has become more common
• not due to tumor• Environmental factors?
Timing of Puberty
• Decreasing age indeveloped countries
• Variation does occurin population
• Various factorscontrolling pubertyonset
Environment & Puberty• Environmental Factors
– health care– personal health improvements– living conditions– socioeconomic standards
• major factors:• photoperiod• nutrition
Photoperiod & Puberty• Photoperiod -
– electricity = 'long days' or a constant summer– light in domestic setting probably not intense
enough to influence photosenstive neuralmechanism in GnRH pathways
– little data to support this hypothesis in humansor primates
Nutrition & Puberty• Nutrition has changed
dramatically in last century• nomadic peoples - Lapps/Saami
– no changes in onset ofmenarche from 1870-1930
– changes occur in villages• diet influences menarche /
normal menstruation– women athletes with low
fat/muscle ratio stopmenstruation
– young girls involved in similaractivities with low fat/hiprotein diets show delayedmenarche or irregularmenstrual cycles
Body Mass & Puberty• onset of menarche is
at 47 kg and hasremained apparentlyunchanged
• critical weight must beattained beforeactivation ofhypothalamo-pituitary-gonadal axis
• suggests 55 kg forboys
Body Mass & Puberty /2
• problem– based on total weight
• (lean body wt + fat, + water)– can this be true?– other factor(s) involved?– most of these studies are retrospective– very difficult to predict puberty by body
weight– menarche /other obvious events occur ‘late’– like the gonadostat hypothesis, this may be a
consequence of puberty not its trigger
Health and Early Puberty1900’s
16 yr - 45 yr = 29 years reproductive lifetime
200012 yr - 50 yr = 38 years reproductive lifetime
29 yr X 12 cycles/yr = 348
38 yr X 12 cycles/yr = 456
Difference = +108 cycles
Health and Early Puberty
348 cycles - (6 pregnancies + 5 lactations)– 348 - (6 X 9 mo + 5 X 12 mo)
456 cycles - (2 pregnancies + 2 lactations)– 456 - (2 X 9 mo + 2 X 6 mo)
348 - (54 + 60) = 234
456 - (18 + 12) = 426
Difference = + 192 cycles55%
PubertyComparative Studies /1
• Comparative Studies– many studies examine puberty in various
domestic species– similar observations of elevated LH/FSH– support for CNS hypothesis– few studies examining puberty in wild
species
PubertyComparative Studies /2
– alligator - male juveniles show clearchange in plasma T at 75 cm TL• sexual maturity at 1 meter SVL
– seasonal variation in plasma T also seen• not all males of this size exhibit elevated T• not uncommon for individuals of a given
population to begin puberty at differing agesor body sizes
PubertyComparative Studies /3
• Few studies have examined seasonalvariation in plasma sex steroids inwild non-mammalian juvenile animals.
• The majority of species examined– (e.g., rodents, salmon, chickens, sheep)– relatively short lives– thus, puberty occurs within a few days
or months and seldom stretches over ayear